Identification of a factor in human milk that can block HIV-1 transmission

Mother to child transmission of HIV accounts for a large proportion of HIV infections in children, with many infected as a result of breastfeeding, which requires transfer of the virus across mucosal barriers. DC-SIGN, a DC lectin receptor, interacts with HIV and is found at high expression levels in tonsillar tissue.

In a paper appearing online on October 20 in advance of print publication of the November issue of the Journal of Clinical Investigation, William Paxton and colleagues from the University of Amsterdam clarify how human milk affects the HIV interactions with DC-SIGN that occur during breastfeeding.

The authors show that human milk can block the binding of HIV to the DC-SIGN molecule expressed on dendritic cells and potently inhibit the transfer of HIV-1 to CD4+ T-lymphocytes. The authors identify the component present in human milk that binds to DC-SIGN. The inhibitory effect can be fully alleviated with an antibody recognizing the Lewis X sugar epitope on this factor. Other major milk proteins do not bind to DC-SIGN nor inhibit viral transfer. These results demonstrate that protein associated Lewis X is necessary and sufficient to interact withDC-SIGN and block the interaction of DC-SIGN and HIV.

The identification of a factor in human milk that can block HIV-1 transmission, the ability of the factor to inhibit the virus from binding to DCs, and the potential immunomodulatory implications of such a compound has major implications for the development of agents that can block HIV transmission.